We plan to devise experiments which will integrate data on structures responsible for T cell activation in the frame of sequential events occurring in differentiation, and of cellular interactions which could lead to the acquisition of the repertoire of specificities: 1. We will try to mimic the intra-thymic differentiation of cells of the T lineage in vitro. The role of SV40 transformed thymic adherent cell lines, in conjunction with lymphokine requirements, will be studied in an effort to dissect the kinetics of the differentiation process. T cell receptor and differentiation antigen gene expression will be studied at various steps of development. Analogous experiments will be carried out on Abelson-virus transformed pre-T cell lines. 2. We will study the structure, gene organization and expression of an Alpha related new mRNA species, "early Alpha" recently identified in our laboratory in early pre-T cells. 3. We will elucidate the genetics, molecular structure, and function of a differentiation antigen (TM.19) recently identified in our laboratory. 4. The functional value of V(D)J TcR-specific Beta and Alpha rearragements will be assessed in transgenic mice. 5. Various aspects of the selection of the adult T repretoire will be investigated: T-T interactions based on the existence of TcR idiotopes which mimic MHC epitopes; in vivo suppression of self-reactive T clonotypes meant to assess the in vivo equivalence of self reactivity. The emergence of a self-restricted T cell repertoire, in ontogeny, and its maintenance in adult T populations is a central problem for both basic and medical immunology. Our porposal aims at contributing to the analysis of this process.